Functional decoding of the human genome is a major challenge. Our focus is to unravel genetic mechanisms and the pathophysiology behind heritable disorders, mainly in traits affecting the central nervous system (CNS). The long term objective is to identify disease associated biomarkers that can be used in search for candidate compounds as a first step in drug development.

Neurodevelopmental and neurodegenerative disorders comprise a heterogeneous group of conditions for which treatment options are limited. Furthermore, the progress in understanding the disease mechanisms has been slow. Obstructing factors are the lack of knowledge on disease-causing molecular mechanisms as well as limited access to biological material and model systems to faithfully recapitulate human pathophysiology. High through-put methods (e.g. next generation sequencing) and induced pluripotent stem cell (iPSC) technologies provide the potential to overcome these problems. To this end, we have established iPSC culture systems that are differentiated into neuronal derivatives to model the pathophysiology behind heritable traits. The iPSCs are derived from patients with various genetic disorders of the CNS (e.g. epilepsy, Down syndrome, Alzheimer disease and specific forms of neurodevelopmental disease), and from healthy individuals. Using high through-put analysis, we have identified several novel disease associated biomarkers that are validated in CRISPR/Cas9 edited iPSC. Selected biomarkers will be adapted to screenable formats using neuronal stem cells and libraries of small compounds.

Astrocyte (green) obtained after 30 day differentiation of induced pluripotent stem cells (iPSC). The iPSC are establihed from a patient with Down syndrome to model the pathophysiology of the central nervous system.